The purpose of this proposal is to explore potential operating mechanisms in the differential sleepiness observed in patients with equivalent degrees of obstructive sleep apnea (OSA). Within a given level of disease severity, i.e., number of respiratory disturbances during sleep, inter-individual differences, or differential vulnerability to sleepiness, have been noted in both subjectively measured and objectively measured daytime sleepiness. The reason for this phenomenon remains unclear. Critical to the management of patients with OSA is the understanding of mechanisms associated with the development of daytime sleepiness. We hypothesize that the variance in daytime sleepiness (EDS)will have a substantial trait component in addition to state-related factors among patients with equivalent levels of OSA severity. To systematically identify sources of EDS variance in sleepy and non-sleepy OSA patients, the specific aims of this study will determine: 1) state-specific variance related to sleep duration, obesity and fat distribution, specific comorbidities, and use of certain medications; 2) mis-estimation of severity of sleep disordered breathing from night-to-night variability in respiratory disturbances; 3) underlying trait associated with differential vulnerability to the sleepiness-producing effects of OSA. Using actigraphy and diaries to document sleep duration and both objective and subjective evaluations of sleepiness, Protocol A will classify 260 newly diagnosed OSA subjects as sleepy vs. non-sleepy and will document inter-individual differences in sleepiness among patients with similar disease severity caused by sleep history, obesity and fat distribution, specific comorbidities, and use of certain medications. Controlling for the variance identified in Protocol A, Protocol B will determine the degree to which inter-individual differences in sleepiness in 180 untreated OSA subjects with similar disease severity is a consequence of night-to-night variability in the occurrence of sleep disordered breathing documented by 7 consecutive nights of home sleep studies. Such night-to-night variability would reduce the reliability of single night determinations of apnea severity. Finally, in Protocol C we will determine if inter-individual differences in sleepiness remain after accounting for the variance explained by the clinical factors identified in Protocol A and the variance explained by mis-estimation of severity of sleep disordered breathing documented in Protocol B. In Protocol C, 60 patients (30 sleepy, 30 non-sleepy) will be matched on initial apnea severity and a set of a priori sleepiness factors will undergo 38 hrs of sleep deprivation in a laboratory to determine the existence of an underlying trait for daytime sleepiness.